{
  "abstract": "Avian influenza poses a persistent pandemic threat, yet traditional vaccines face production delays. Self-amplifying mRNA (sa-mRNA) technology offers potential advantages, including rapid development, dose sparing, and enhanced, durable immunity. We evaluated ARCT-2304, a bicistronic sa-mRNA vaccine encoding H5N1 hemagglutinin (HA) and neuraminidase (NA), in a Phase 1 randomized, observer-blind trial (NCT06602531). Healthy adults (N = 212) received two doses of ARCT-2304 (1.5, 5, or 12 mcg) or control/placebo on a 4- or 8-week schedule. Primary outcomes evaluated safety and reactogenicity (solicited/unsolicited/serious adverse events [AEs]) and immunogenicity (HA inhibition and NA enzyme-linked lectin assays 28 days post-second dose). Immunogenicity results were benchmarked using serum from a prior study supporting licensure of an H5N1 vaccine. ARCT-2304 was well-tolerated, displaying mostly mild-to-moderate, transient, dose-dependent solicited AEs, with no safety concerns identified. Two doses elicited robust HA and NA humoral responses. An 8-week interval yielded higher magnitude and greater durability than a 4-week schedule, with neutralizing and anti-NA antibodies remaining significantly elevated 6–7 months post-second dose. ARCT-2304 also induced dose-dependent, Th1-polarized T-cell responses peaking at Day 29. These findings support advancing sa-mRNA platforms for pandemic influenza preparedness.",
  "abstract_shown": true,
  "affiliations": [
    "CTI Clinical Trial and Consulting Services, Covington, Kentucky USA",
    "Arcturus Therapeutics, San Diego, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Antoinette A. Pragalos"
    },
    {
      "affs": [
        1
      ],
      "name": "Filippo Pacciarini"
    },
    {
      "affs": [
        1
      ],
      "name": "Hongfan Jin"
    },
    {
      "affs": [
        1
      ],
      "name": "Terri Hopkins"
    },
    {
      "affs": [
        1
      ],
      "name": "Ye Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Roberto Bugarini"
    },
    {
      "affs": [
        1
      ],
      "name": "Xuexuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Brian M. Sullivan"
    },
    {
      "affs": [
        1
      ],
      "name": "Carole Verhoeven",
      "orcid": "0009-0000-7935-7050"
    },
    {
      "affs": [
        1
      ],
      "name": "Igor Smolenov",
      "orcid": "0000-0002-7075-9827"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/00ckqwa02ztvf.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78031-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696684/",
  "id": "00ckqwa02ztvf",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-78031-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2713|Influenza Virus Research Studies"
    ]
  ],
  "openalex": "W7214245466",
  "pdf_url": "https://europepmc.org/articles/PMC13696684?pdf=render",
  "pmcid": "PMC13696684",
  "pmid": "42928290",
  "published": "2026-09-24",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/00ckqwa02ztvf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:00Z",
      "native_id": "PMC13696684",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78031-9"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928290",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928290"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Influenza Virus Research Studies",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Extended dosing intervals enhance the durability of a self-amplifying mRNA vaccine against pandemic H5N1 influenza: a randomized, observer-blind, dose-finding Phase I study",
  "title_text": "Extended dosing intervals enhance the durability of a self-amplifying mRNA vaccine against pandemic H5N1 influenza: a randomized, observer-blind, dose-finding Phase I study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:59Z",
  "url": "https://research.draconitic.com/paper/00ckqwa02ztvf",
  "venue": "Nature Communications",
  "versions": []
}